Author Correction: The axolotl genome and the evolution of key tissue formation regulators

Salamanders serve as important tetrapod models for developmental, regeneration and evolutionary studies. An extensive molecular toolkit makes the Mexican axolotl (Ambystoma mexicanum) a key representative salamander for molecular investigations. Here we report the sequencing and assembly of the 32-gigabase-pair axolotl genome using an approach that combined long-read sequencing, optical mapping and development of a new genome assembler (MARVEL). We observed a size expansion of introns and intergenic regions, largely attributable to multiplication of long terminal repeat retroelements. We provide evidence that intron size in developmental genes is under constraint and that species-restricted genes may contribute to limb regeneration. The axolotl genome assembly does not contain the essential developmental gene Pax3. However, mutation of the axolotl Pax3 paralogue Pax7 resulted in an axolotl phenotype that was similar to those seen in Pax3-/- and Pax7-/- mutant mice. The axolotl genome provides a rich biological resource for developmental and evolutionary studies.

[1]  D. Haussler,et al.  Ultraconserved Elements in the Human Genome , 2004, Science.

[2]  R. Sperry Effect of 180 degree rotation of the retinal field on visuomotor coordination , 1943 .

[3]  B. King,et al.  A Conserved MicroRNA Regulatory Circuit Is Differentially Controlled during Limb/Appendage Regeneration , 2016, PloS one.

[4]  M. Capecchi,et al.  Absence of radius and ulna in mice lacking hoxa-11 andhoxd-11 , 1995, Nature.

[5]  Cynthia Alexander Rascón,et al.  Comparative Transcriptional Profiling of the Axolotl Limb Identifies a Tripartite Regeneration-Specific Gene Program , 2013, PloS one.

[6]  S. Voss,et al.  Salamander Hox clusters contain repetitive DNA and expanded non-coding regions: a typical Hox structure for non-mammalian tetrapod vertebrates? , 2013, Human Genomics.

[7]  J. von Hofsten,et al.  Pax7 is required for establishment of the xanthophore lineage in zebrafish embryos , 2016, Molecular biology of the cell.

[8]  H. Spemann,et al.  über Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren , 1924, Archiv für mikroskopische Anatomie und Entwicklungsmechanik.

[9]  S. Odelberg,et al.  A transitional extracellular matrix instructs cell behavior during muscle regeneration. , 2010, Developmental biology.

[10]  M. Rudnicki,et al.  Distinct roles for Pax7 and Pax3 in adult regenerative myogenesis , 2006, The Journal of cell biology.

[11]  E. Tanaka,et al.  Progressive Specification Rather than Intercalation of Segments During Limb Regeneration , 2013, Science.

[12]  Colin N. Dewey,et al.  Comparative RNA-seq Analysis in the Unsequenced Axolotl: The Oncogene Burst Highlights Early Gene Expression in the Blastema , 2013, PLoS Comput. Biol..

[13]  Maritta Schuez,et al.  Live Imaging of Axolotl Digit Regeneration Reveals Spatiotemporal Choreography of Diverse Connective Tissue Progenitor Pools , 2016, Developmental cell.

[14]  S. Voss,et al.  Initial characterization of the large genome of the salamander Ambystoma mexicanum using shotgun and laser capture chromosome sequencing , 2015, Scientific Reports.

[15]  A. Meyer,et al.  Evolution of the Vertebrate Pax4/6 Class of Genes with Focus on Its Novel Member, the Pax10 Gene , 2014, Genome biology and evolution.

[16]  Steven J. M. Jones,et al.  Improved white spruce (Picea glauca) genome assemblies and annotation of large gene families of conifer terpenoid and phenolic defense metabolism. , 2015, The Plant journal : for cell and molecular biology.

[17]  José M. Sempere,et al.  The Gypsy Database (GyDB) of mobile genetic elements: release 2.0 , 2010, Nucleic Acids Res..

[18]  Timothy L. Tickle,et al.  A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors. , 2017, Cell reports.

[19]  S. Voss,et al.  Ambystoma mexicanum, the axolotl: a versatile amphibian model for regeneration, development, and evolution studies. , 2009, Cold Spring Harbor protocols.

[20]  J. Brockes,et al.  Evidence for the local evolution of mechanisms underlying limb regeneration in salamanders. , 2010, Integrative and comparative biology.

[21]  R. Auerbach Analysis of the developmental effects of a lethal mutation in the house mouse , 1954 .

[22]  Jun Wang,et al.  Whole-genome sequence of the Tibetan frog Nanorana parkeri and the comparative evolution of tetrapod genomes , 2015, Proceedings of the National Academy of Sciences.

[23]  Ahmed Mansouri,et al.  Divergent functions of murine Pax3 and Pax7 in limb muscle development. , 2004, Genes & development.

[24]  E. Tanaka The Molecular and Cellular Choreography of Appendage Regeneration , 2016, Cell.

[25]  Wei Zhu,et al.  Genic regions of a large salamander genome contain long introns and novel genes , 2009, BMC Genomics.

[26]  Colin N. Dewey,et al.  Analysis of embryonic development in the unsequenced axolotl: Waves of transcriptomic upheaval and stability. , 2017, Developmental biology.

[27]  Anoop Kumar,et al.  An orphan gene is necessary for preaxial digit formation during salamander limb development , 2015, Nature Communications.

[28]  Steven L Salzberg,et al.  The first near-complete assembly of the hexaploid bread wheat genome, Triticum aestivum , 2017, bioRxiv.

[29]  P. B. Gates,et al.  The newt ortholog of CD59 is implicated in proximodistal identity during amphibian limb regeneration. , 2002, Developmental cell.

[30]  P. Gruss,et al.  Dysgenesis of cephalic neural crest derivatives in Pax7-/- mutant mice. , 1996, Development.

[31]  R. Tassava,et al.  Extracellular matrix protein turnover during salamander limb regeneration , 1996, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[32]  R. Mueller,et al.  LTR Retrotransposons Contribute to Genomic Gigantism in Plethodontid Salamanders , 2011, Genome biology and evolution.

[33]  P Gruss,et al.  Pax genes and their roles in cell differentiation and development. , 1996, Current opinion in cell biology.

[34]  R. Mueller,et al.  Hellbender Genome Sequences Shed Light on Genomic Expansion at the Base of Crown Salamanders , 2014, Genome biology and evolution.

[35]  S. Salzberg,et al.  An improved assembly of the loblolly pine mega-genome using long-read single-molecule sequencing , 2017, GigaScience.

[36]  J. Epstein,et al.  Identification of minimal enhancer elements sufficient for Pax3 expression in neural crest and implication of Tead2 as a regulator of Pax3 , 2004, Development.

[37]  Keith Bradnam,et al.  CEGMA: a pipeline to accurately annotate core genes in eukaryotic genomes , 2007, Bioinform..

[38]  R. Barsacchi,et al.  MARCKS-Like Protein is an Initiating Molecule in Axolotl Appendage Regeneration , 2016, Nature.

[39]  Li Li,et al.  Distinct enhancers at the Pax3 locus can function redundantly to regulate neural tube and neural crest expressions. , 2010, Developmental biology.

[40]  C. Barbas,et al.  ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. , 2013, Trends in biotechnology.